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Significance of Some Proliferation Markers and Some Prognostic Factors in Patients with Multiple Myeloma and their Impact on the Patients' Survival

  • Abdelgawad, Iman A. (Clinical Pathology department, NCI, Cairo University) ;
  • Radwan, Noha H. (Clinical Pathology department, NCI, Cairo University) ;
  • Shafik, Roxan E. (Clinical Pathology department, NCI, Cairo University) ;
  • Shokralla, Hala A. (Medical Oncology department, NCI, Cairo University)
  • Published : 2016.05.01

Abstract

Background: Multiple myeloma (MM) is influenced by genetic and micro-environmental changes. Malignant plasma cells produce an abnormal monoclonal immunoglobulin, as well as cytokines, such as IL-10 and IL-6 which stimulate cells of the bone marrow microenvironment (BMM) and cause dysfunction and failure of many organs. B cell activating factor (BAFF), IL6, IL10 are known to influence the growth & survival of the malignant clone. Aim: The objectives of the present study were to investigate the circulating levels of BAFF, IL-10 and IL-6, correlate them with well-known parameters of disease activity in patients with MM, and to detect their impact on the patients' survival. Materials and Methods: This study was conducted on 89 newly diagnosed MM patients and seventy apparently healthy volunteers as a normal control group. BAFF, IL6, IL10 were measured by ELISA for both groups. Survival analysis was performed for all patients. Results: Studied markers were higher in the MM patients compared to the normal control subjects. Patients' survival was improved by high serum BAFF levels. Conclusions: High levels of BAFF were found to improve patients' survival. BAFF and IL-6 can be considered probable diagnostic markers for MM.

Keywords

Multiple myeloma;BAFF;IL6;IL10

References

  1. Aarden L, DeGroot E, Schaap O, et al (1987). Production of hybridoma growth factor by human monocytes. Eur J Immunol, 17, 14116.
  2. Alexandrakis M, Roussou P, Pappa C, et al (2013). Relationship between Circulating BAFF Serum Levels with Proliferating Markers in Patients with Multiple Myeloma. Biomed Res Int, 389579.
  3. Batten M, Groom J, Cachero G, et al (2000). BAFF mediates survival of peripheral immature B lymphocytes. J Exp Med, 192, 1453-66. https://doi.org/10.1084/jem.192.10.1453
  4. Bird M, Owen G, D'Sa S, et al (2011). Guidelines for the diagnosis and management of multiple myeloma. Br J Haematol, 154, 3275.
  5. Bradwell R, CarrSmith D, Mead P, et al (2001). Highly sensitive, automated immunoassay for immunoglobulin free light chains in serum and urine. Clin Chem, 47, 67380.
  6. Caers J, Van Valckenborgh E, Menu E, et al (2008). Unraveling the biology of multiple myeloma disease: cancer stem cells, acquired intracellular changes and interactions with the surrounding microenvironment. Bull Cancer, 95, 301-13.
  7. Carl A, Burtis, Edward R, et al (1999). Tietz Text book of clinical chemistry, 3rd Ed, Philadelphia : W.B. Saunders 1400.
  8. Durie G, Kyle A, Belch A, et al (2003). Myeloma management guidelines: a consensus report from the scientific advisors of the international myeloma foundation. Hematol J, 4, 37998.
  9. DuVillard L, Guiguet M, Casasnovas O, et al (1995). Diagnostic value of serum IL6 level in monoclonal gammopathies. Br J Haematol, 89, 2439.
  10. Estimated Cancer Incidence, Mortality and Prevalence in (2012). Available at http://globocan.iarc.fr/Pages/fact_sheets_population.aspx. Accessed: May 2014.
  11. Fragioudaki M, Boula A, Tsirakis G, et al (2012). B cellactivating factor: its clinical significance in multiple myeloma patients. Ann Hematol, 91, 14138.
  12. Greipp R, San Miguel J, Duries M, et al (2005). International Staging System for multiple myeloma. J Clin Oncol, 23, 341220.
  13. Gupta M, Han J, Stenson M, et al (2012). Elevated serum IL10 levels in diffuse large Bcell lymphoma: a mechanism of aberrant JAK2 activation. Blood, 119, 2844-53. https://doi.org/10.1182/blood-2011-10-388538
  14. Hengeveld J , Kersten J (2015). Bcell activating factor in the pathophysiology of multiple myeloma: a target for therapy? Blood Cancer J, 27, 282.
  15. Hirano T (2014). Revisiting the 1986 molecular cloning of interleukin 6. Front. Immunol, 5, 456.
  16. Horii Y, Muraguchi A, Suematsu S, et al (1988). Regulation of BSF2/IL6 production by human mononuclear cells. J Immunol, 141, 152935.
  17. Kim E, Yoo C, Lee H, et al (2010). Serum albumin level is a significant prognostic factor reflecting disease severity in symptomatic multiple myeloma. Ann Hematol, 89, 3917.
  18. Kovacs E (2010). Interleukin6 leads to interleukin10 production in several human multiple myeloma cell lines. Several human multiple myeloma cell lines. Does interleukin10 enhance the proliferation of these cells? Leuk Res, 34, 912-6. https://doi.org/10.1016/j.leukres.2009.08.012
  19. Kyle A, Gertz A, Witzig E, et al (2003). Review of 1027 patients with newly diagnosed multiple myeloma. Mayo Clin Proc, 78, 2133.
  20. Lauta M (2003). A review of the cytokine network in multiple myeloma. Cancer, 97, 2440-52. https://doi.org/10.1002/cncr.11072
  21. Lemancewicz D, Bolkun L, Jablonska E, et al (2013). Evaluation of TNF superfamily molecules in multiple myeloma patients:Correlation with biological and clinical features. Leuk Res, 37, 108993.
  22. Moore W, O'Garra A, de Waal R, et al (1993). Interleukin10. Annu Rev Immunol, 11, 16590.
  23. Moreaux J, Legouffe E, Jourdan E, et al (2004). BAFF and APRIL protect myeloma cells from apoptosis induced by interleukin 6 deprivation and dexamethasone. Blood, 103, 3148-57. https://doi.org/10.1182/blood-2003-06-1984
  24. Moreau P, San Miguel J, Ludwig H, et al (2013). Multiple Myeloma: ESMO Clinical Practice Guidelines, Ann Oncol, 24, 1337.
  25. Multiple Myeloma: Statistics (2015). Available at: http://www.cancer.net/cancertypes/multiplemyeloma/statistics.
  26. Okada M, Kitahara M, Kishimoto S, et al (1988). I16/BSF2 functions as a killer helper factor in the in vitro induction of cytotoxic T cells. J Immunol, 141, 1543-9.
  27. Oken M, Creech H, Tormey C, et al (1982). Toxicity And Response Criteria Of The Eastern Cooperative Oncology Group. Am J Clin Oncol, 5,64955.
  28. Pika T, Minarik J, Schneiderka P, et al (2008).The correlation of serum immunoglobulin free light chain levels and selected biological markers in multiple myeloma. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub, 152, 61-4. https://doi.org/10.5507/bp.2008.009
  29. Sirohi B, Powles R, Kulkarni S, et al (2001). Comparison of new patients with Bence Jones, IgG and IgA myeloma receiving sequential therapy: the need to regard these immunologic subtypes as separate disease entities with specific prognostic criteria. Bone Marrow Transplant, 28, 2937.
  30. Sirohi B, Powles R (2004). Multiple myeloma. Lancet, 363, 87587.
  31. Solomon A (1976). BenceJones proteins and light chains of immunoglobulins (first of two parts). N Engl J Med, 294, 17-23. https://doi.org/10.1056/NEJM197601012940105
  32. Solomon A (1986). Clinical implications of monoclonal light chains. Semin Oncol, 13, 3419.
  33. Tinhofer I, Marschitz I, Henn T, et al (2000). Expression of functional interleukin15 receptor and autocrine production of interleukin15 as mechanisms of tumor propagation in multiple myeloma. Blood, 95, 610-8.
  34. Tricot G (2000). New insights into the role of microenvironment in multiple myeloma. Lancet, 355, 24850.
  35. Weissenbach J, Chernajovsky Y, Zeevi M, et al (1980). Two interferon mRNAs in human fibroblasts: In vitro translation and Escherichia coli cloning studies. Proc Natl Acad Sci USA, 77, 7152 6. https://doi.org/10.1073/pnas.77.12.7152
  36. Wang M, Zhang L, Jiang M, et al (2011). Expression and significance of B cellactivating factor of TNF family (BAFF) and B cell lymphoma/leukemia2 (BCL2) in multiple myeloma. Zhongguo Shi Yan Xue Ye Xue Za Zhi, 19, 3958.